Progressive multifocal leukoencephalopathy and sphingosine 1-phosphate receptor modulators used in multiple sclerosis: an updated review of literature

Objective Progressive multifocal leukoencephalopathy (PML) is a serious viral infection associated with disease-modifying therapies (DMT) for multiple sclerosis (MS) including sphingosine 1-phosphate receptor (S1PR) modulators. The objective of this review was to investigate the characteristics of PML in MS patients associated with drugs of the S1PR modulator. Methods We conducted a literature review and analysis of 24 patients from 12 publications in PubMed, SCOPUS and EMBASE. This is a descriptive analysis and study of characteristics of PML associated fingolimod and related S1PR modulator group of DMT. Results A total of 24 cases of PML in MS patients treated with fingolimod were identified. Of these, 21 cases contained data regarding changes in the expanded disability status scale (EDSS). One case of PML in association with ozanimod treatment in a clinical trial was also identified. In PML cases associated with fingolimod, the mean age at the time of PML diagnosis was 50.91 +/- 11.5 years. All patients were treated with fingolimod for more than 24 months. Compared to patients who improved or were stable, in terms of EDSS, after symptomatic management of PML, the non-improved groups were significantly older. There were no fatalities in either group during the reported follow-up period. Conclusion The incidence of PML appears to be extremely low in MS patients treated with S1PR modulators. Risk of PML increases with increase in duration of treatment with S1PR modulators like fingolimod, and increased age at the time of PML diagnosis is associated with worse prognosis.

Automated summary

The incidence of PML in MS patients treated with S1PR modulators like fingolimod appears to be extremely low. Risk of PML increases with longer duration of treatment with S1PR modulators, and older age at the time of PML diagnosis is associated with worse prognosis.